Peptides comprised of a relatively low number of amino acid residues, yet which possess therapeutic activity, are known in the art. For example, Okai Japanese Patent No. 63-215697 (unexamined) discloses peptides containing at least five amino acid residues which are stated to have muscle relaxant activity. The type of muscle relaxant activity possessed by the disclosed peptides is not given.
Gieger, et al., U.S. Pat. No. 4,623,715, discloses peptides containing four or more amino acid residues, preferably pentapeptides and hexapeptides, which are useful as mood-elevators, antidepressants and anxiolytic agents.
Gormley, U.S. Pat. No. 4,421,744, discloses peptides and pseudo-peptides of the formula (R).sub.2 N-A-B-D-E-F-X wherein A and F are amino acid residues, and each of B, D and E can be an amino acid residue or a valency bond. These compounds are active as opiate receptor agonists.
Wilkinson, U.S. Pat. No. 4,254,106, discloses N,N-dialkyl, i.e. N-terminal tertiary, peptides containing at least five amino acid residues which are useful as morphine agonists.
Kahn et al. Tetrahedron Letters, Vol. 27, No. 40, pp 4841-4844, (1986), and Najjar, U.S. Pat. No. 3,778,426, disclose peptides which mimic the activity of the naturally occurring tetrapeptide tuftsin which is an immunostimulant.
Kouge et al. Bulletin of the Chemical Society of Japan, Vol. 60, pp 4343-4349 (1987) and Peptide Chemistry 1986. Proceedings of the 24.sup.th Japanese Symposium on Peptide Chemistry. T. Shiba ed. Osaka: Protein Research Foundation; pp. 229-232 (1987) disclose several tetrapeptides that contract and relax the anterior byssus retractor muscle of molluscs depending on the concentration administered. The peptides exhibit their modulatory effects by acting at specific presynaptic receptors in the molluscan muscle. In contrast, the known mammalian skeletal muscle relaxants act as agonists (depolarizing) or antagonists (non-depolarizing) at the postsynaptic nicotinic acetylcholine receptor.
Matsuo et al., U.S. Pat. No. 4,904,763, discloses several cysteine-bridged peptides, containing at least twenty amino acids, that induce relaxation of mammalian vascular smooth muscle.
Sakakibara, Chem. Abstr., Vol. 105:43332p and Chem. Abstr., Vol. 105:97955n disclose several dodeca-, trideca-, and tetradecapeptide derivatives of the conotoxins with skeletal muscle relaxant activity comparable to that of a tubocurarine derivative. The peptides contain at least two disulfide bridges which are necessary to lock the constituent amino acids in the proper conformation for bioactivity.
In accordance with the present invention, it has been found that certain tripeptides possess significant nondepolarizing muscle relaxant activity, thus making them useful therapeutically as skeletal muscle relaxants.